Means and composition for the stabilization of divinyl ether



Patented June 23, 1936 am no stares PATENT OFFICE 2,044,800 MEANS AND COMPOSITION ron 'rnn STABILIZATION or nrvnnn. ETHER Randolph '1. Major, Mountainside, and William L. Ruigh, Metuchen, N. 3., assignors to Merck & 00.. Inc., litahway, N. 5., a corporation of New Jersey No Drawing. Application June 21, 1933, Serial No. 676,926-

'9 Claims. (01. 23-250) processes for producing it in highly pure form vinyl ether, etc.

which renders it useful for many technical purposes and for anesthesia.

The process for producing this pure divinyl ether, as described in the said copending application, comprises the steps of reacting upon ,9, 13' dihalogen-diethyl ether with alkali hydroxide in an autoclave under constant stirring to prevent the formation of any crust of alkali upon the surface of the reaction mixture, using appropriate distillation and condensation means, and passing a stream of ammonia gas throughout the reaction, distilling and condensing systems during the conduct of the entire process. The process thus set forth produces as a final product a divinyl ether substantially free from aldehyde, ethylene oxide, 1, 4-dioxane, p-chloroethyl- In this manner, we were able to produce and isolate for the first time a true divinyl ether showing decidedly different physical constants from the preparations which had theretofore been produced in the belief that they were divinyl ether. Thus, while various products which had hitherto been described as divinyl ethers had shown a wide range of boiling points from, say, 34 to 39 C., the new product resulting from our process described was found to be a volatile, colorless liquid, boiling at about 28.3:03" C, at 760 mm., having a density of d 0.774 and d 0.773 and a refractive index N 1.3989. v These findings, together with analyses and molecular weight determinations, clearly distinguished our new product from those described in the Oldliterature, and indicated that it is substantially pure C2H3.O.C2H3.

Based upon the pharmacological studies of Leake and Chan (Proc. Soc. Exper. Biol. and Med., 1930, mVIII) of the anesthetic properties of unsaturated ethers, this product, therefore, was indicated on theoretical grounds to be a promising new anesthetic, especially because it was in highly pure form and contained no injurious by-products, such as'aldehyde, ethylene oxide, 1, 4-dioxane, and fi-chloroethyl-vinyl ether, which are present in the products prepared by the old methods. Recent clinical results have justified the theoretical conceptions as to relatively low toxicity and anesthetically important physical and chemical properties.

80, also, the new product readily lends itself to numerous technical uses-for instance as a solvent for fats, oils and waxes, and for their extraction, and as an intermediate in the preparation of various solid and semi-solid glass-like 5 polymers. On account of its definite composition and properties, it is susceptible to more positive and reliable adaptation, to its several possible uses, as compared with the hitherto lmown preparation of indefinite and varying composi- 10 tion. These advantages are ascribable to the fact that true divinyl ether contains no higher boiling material and no active foreign material,

such as acetaldehyde, which reacts with many 15 compounds.

However, it has been found that this new true divinyl ether is prone to decomposition when it is exposed for a time to atmospheric air, with oxidation to peroxides, aldehydes, and acids, and

it also readily polymerizes under conditions of 20 such exposure, especially when in a warm place and in the light. Such decomposition, deterioration and polymerization obviously render the ether unfit, not

only for anesthetic uses, but for general'techni- 25 cal uses as a solvent and otherwise as well.

It has now been found by us that this new pure unsaturated ether can be effectively protected for practical periods by adding a suitable 0 inhibitor. We have found that groups of substances which satisfactorily inhibit decomposition are various polyphenols, ammonia, and phenolic and non-phenolic aromatic amines. We have found as especially satisfactory, accord-- ing to the ultimate requirements, such compounds as hydroquinone and py ogallol, ammonia, antipyrine, quinine, phenyl-a-naphthylamine, phenyl-p-naphthylamine, o-nitroaniline, p-phenylene-diamine, p-toluidine, diphenylenediamine, p-nitrophenylhydrazine, p-aminophenol, N-methylaminophenol, N-isopropylaminophenol, etc.

For anesthetic purposes, such aromatic amines and. the like must, of course, also be relatively 45 non-toxic in the quantities employed, and nonvolatile. For technical uses of the ether, the chosen inhibitor must be chemically inert for the specific purposes of the use. Such limitations and appropriate selections will be readily under- 0 stood according to the nature of the materials coming into consideration.

To further protect the other from decomposition or deterioration, it is also desirable that the vinyl ether be sealed in vacuo or in an atmosphere Of 55 an inert gas such as nitrogen.

The practical application of the process for the production oi. a stabilized dlvinyl ether comprises the solution of the given appropriate inhibitor in approximately from one part to 100 parts, to as low as one part per 100,000 parts of the ether. Obviously the inhibiting action of these several agents is in general more certain and positive with the relative increase in quantity within reasonable limits, and the specific material selected, as well as the quantities used, may be conveniently modified to adapt the process to the special requirements as indicated.

Thus, in the special case of preparing the divinyl ether for use as a general anesthetic, the inhibiting agent is preferably such a substance as phenyl-anaphthylamine, because of its relatively low toxicity. This low toxicity again in turn makes it possible to employ relatively larger proportional quantities to-insure more positive stabilization. Very satisfactory results have been obtained for this purpose by adding one part of phenylanaphthylarnine to 10,000 parts of the ether, al-

f though this latter inhibitor exercises a demonstrable inhibitory efiect in concentrations as low as 1:100,00-0.

v As a general guide for the quantitative determinations as directed to various practical applinitroaniline, antipyrine, p-phenylenediamine, p-

toluidine, .diphenylenediamine, p-nitrophenylhydrazine, quinine, p-aminophenol, N-methylaminophenol, and N-isopropylaminophenol.

The following inhibitors have been used in concentrations as low as 1:50,000 with appreciable efl'ect: p-phenylenediamine, a-phenylnapht'nylamine, hydroquinone, and p-aminophenol.

The further steps of the process comprising the packaging of the material in vacuo or with an atmosphere of nitrogen, for instance, if required, may be practiced by any of the known or convenient methods.

It is desirable, also, especially in the case of divinyl. ether, stabilized in the manner indicated when intended for general anesthetic use, to add a quantity of an anti-freeze agent, which, for

such uses, should be non-toxic, soluble in the di-,

vinyl ether and in water, and volatile in the mixture with the ether. Such an agent is available, for example, in ethyl alcohol, where it has been found that a quantity of about 3.5% by volume is generally sufiicient. The quantity of ethyl alco- 1101 for serving as an antifreeze agent with the vinyl ether has been found to range from about 1.5% to about 5%. Excessive quantities of alcohol are to be avoided to prevent the collection of unevaporatedalcohol on the ether cone or mask.v

,The present application will be limited in its claims to the methods of stabilization and stabilizing agents disclosed. A divisional application filed September 7, 1933, Serial No. 688,462 has been filed by us to cover more particularly the production of a divinyl ether especially suitable for general anesthetic purposes, comprisingthe divinyl ether with appropriate stabilizing substances and an appropriate antifreeze ingredient, substantially as described.

We claim as new:

'1. Divinyl ether stabilized with an aromatic amine.

2. Divinyl ether stabilized with an alkyl aryl amine.

3. Divinyl ether stabilized with a diarylamine.

4. Divinyl ether stabilized with N, N-diphenyl phenylene diamine.

5. Divinyl ether stabilized with N-phenyl-mnaphthylamine.

6. A stabilized divinyl ether solution containing substantially one part of an aromatic amine to from 100 to 100,000 parts of the ether.

7. The process'of inhibiting polymerization of divlnyl ether which consists of dissolving therein one part of an aromatic amine to from 100 to 100,000 parts of the ether.

8. The process of stabilizing divinyl ether comprising the step of dissolving therein an aromatic amine.

9. The method of preserving and packaging divinyl ether which consists of dissolving therein one part of an aromatic amine to'from 10,000 to 100,000 parts of the ether and packaging the same in vacuo or with an atmosphere of an inert gas such as nitrogen.

RANDOLPH T. MAJOR. WILLIAM L. RUIGH. 

